Clinical efficacy and safety of anti-PD-1 antibody combined with pegaspargase for patients of relapsed or refractory NK/T cell lymphoma
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摘要: 目的 探讨PD-1单抗联合培门冬酶在复发难治结外NK/T细胞淋巴瘤，鼻型(ENKTCL)患者中的临床疗效和安全性。方法 回顾性分析我院初治采用P-GEMOX联合或不联合放疗治疗后复发难治的13例ENKTCL患者的临床资料，探讨其临床特点及PD-1单抗联合培门冬酶作为解救治疗方案的疗效和安全性。结果 13例患者中男10例，女3例；中位年龄52(17~74)岁；Ann-Arbor分期：ⅡEA期3例，ⅡEB期4例，ⅢEB期1例，ⅣEA期1例，ⅣEB期4例；PINK-E评分：1分1例，2分7例，3分5例；乳酸脱氢酶高于正常值(>245 U/L)10例，鼻外病变7例。13例患者在复发和疾病进展时出现骨髓受累1例，合并噬血细胞综合征2例。所有患者中位随访时间9(3~24)个月，8例患者仍处于完成缓解。接受P-GEMOX方案治疗的中位疗程数为3(2~10)个，接受PD-1单抗联合培门冬酶治疗的中位疗程数为7(2~11)个。截至随访终点，共9例患者存活，死亡4例，均死于疾病复发和进展导致的多脏器功能衰竭。4例死亡患者复发到死亡的中位生存时间为6.5(3~13)个月。13例患者中完全缓解8例，部分缓解1例，疾病进展4例，总反应率69.2%，完全缓解率61.5%，部分缓解率7.7%。最常见的不良反应为乏力6例(46.2%)，发热5例(38.5%)，肺炎4例(30.8%)，甲状腺功能减退3例(23.1%)，急性胰腺炎1例(7.7%)。结论 PD-1单抗联合培门冬酶在复发难治ENKTCL患者的近期疗效好，耐受性好，可作为复发难治ENKTCL的挽救治疗方案。Abstract: Objective To explore the therapeutic effects and safety of anti-PD-1 antibody combined with pegaspargase in patients with relapsed or refractory extranodal NK/T cell lymphoma(ENKTCL).Methods Clinical data of 13 patients with relapsed or refractory ENKTCL who were initially treated with P-GEMOX combined with or without radiotherapy in our hospital were retrospectively analyzed, in order to explore their clinical characteristics and the efficacy and safety of anti-PD-1 antibody combined with pegaspargase as rescued therapy.Results Among the 13 patients, 10 cases were male and 3 cases were female, with a median age of 52(17-74) years. The Ann-Arbor staging system was 3 cases of stage ⅡEA, 4 cases of stage ⅡEB, 1 case of stage ⅢEB, 1 case of stage ⅣEA, 4 cases of stage ⅣEB. PINK-E scoring system was 1 point in 1 case, 2 points in 7 cases, 3 points in 5 cases. Lactate dehydrogenase was higher than normal(>245 U/L) in 10 cases. Extranasal lesions were observed in 7 cases. Among the 13 patients, bone marrow involvement occurred in 1 case and hemophagocytic syndrome in 2 cases. The median follow-up time for all patients was 9(3-24) months, and 8 patients were still in complete remission. The median number of courses of treatment with P-GEMOX was 3(2-10). The median number of courses of treatment with sintilimab combined with pegaspargase was 7(2-11). By the end of follow-up, 9 cases survived and 4 cases died, all of which died of multiple organ failure due to disease recurrence and progression. The median survival time from relapse to death was 6.5(3-13) months in the 4 patients who died. Of the 13 patients, 8 cases achieved complete response, 1 case achieved partial response, and 4 cases were disease progression. The total response rate was 69.2%, the complete response rate was 61.5%, and the partial response rate was 7.7%. The most common adverse events were fatigue in 6 cases(46.2%), fever in 5 cases(38.5%), pneumonia in 4 cases(30.8%), hypothyroidism in 3 cases(23.1%), and acute pancreatitis in 1 case(7.7%).Conclusion Anti-PD-1 antibody combined with pegaspargase has a good short-term efficacy and tolerability in patients with relapsed and refractory ENKTCL, and can be used as a rescue treatment for relapsed and refractory ENKTCL.
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Key words:
- extranodal NK/T cell lymphoma /
- relapsed /
- refractory /
- anti-PD-1 antibody /
- sintilimab /
- pegaspargase
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表 1 13例复发难治ENKTCL患者的临床资料及治疗方案
例号 性别 年龄/岁 初始治疗 复发难治治疗 原发部位 分期 EBER EBV-DNA/(copies·mL-1) 乳酸脱氢酶/(U·L-1) PINK-E
评分Ki-67/% 治疗方案 部位 疗程 转归 1 男 24 鼻腔、肺、右眼内直肌 ⅣEB 阳性 2.78×103 493 3 90 P-GEMOX×2 肺 7 CR 2 男 51 鼻腔 ⅡEB 阳性 阴性 586 1 80 GEMOX×4+鼻腔放疗 皮肤 7 CR 3 女 52 骨、双肾、子宫 ⅣEB 阳性 3.48×104 316 3 90 P-GEMOX×6 骨 2 死亡 4 男 60 鼻腔 ⅡEB 阳性 5.00×104 205 2 70 P-GEMOX×2 骨髓 3 PR 5 男 66 皮肤 ⅢEB 阳性 阴性 317 2 80 P-GEMOX×10 骨 7 死亡 6 男 23 鼻腔 ⅡEA 阴性 4.70×103 298 2 80 P-GEMOX×6 鼻腔 3 CR 7 男 74 鼻腔 ⅡEB 阳性 1.00×103 340 2 70 P-GEMOX×2 鼻腔、发热 3 CR 8 男 17 鼻腔、上颌窦、淋巴结 ⅣEB 阳性 3.80×104 747 3 70 P-GEMOX×3 鼻腔、噬血 11 死亡 9 女 43 肝脏、淋巴结 ⅣEB 阳性 1.40×106 3162 3 80 P-GEMOX×2 淋巴结 8 CR 10 男 68 鼻腔 ⅡEA 阴性 1.20×103 294 3 90 P-GEMOX×4+鼻腔放疗 鼻腔 5 CR 11 男 39 皮肤 ⅣEA 阳性 阴性 152 2 80 P-GEMOX×3 皮肤 8 CR 12 女 52 肺 ⅡEA 阳性 阴性 214 2 80 P-GEMOX×6 肺 7 CR 13 男 52 鼻腔 ⅡEB 阳性 2.30×103 791 2 70 P-GEMOX×2 鼻腔、噬血 4 死亡 
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